Takeda Announces FDA Accelerated Approval of Alunbrig

Takeda Pharmaceutical announced Alunbrig has received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Alunbrig, which previously received Breakthrough Therapy Designation from the FDA, is a once-daily oral therapy that may be taken with or without food.

"In recent years, small molecule ALK inhibitors have revolutionized the treatment options for those with advanced ALK+ non-small cell lung cancer. Nevertheless, there is still a need for additional ALK inhibitors like Alunbrig, which have a manageable safety profile and may address mechanisms of clinical resistance to crizotinib, including progression in the central nervous system," D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado said. "The ALTA trial showed that Alunbrig was highly effective post-crizotinib with the majority of patients who received 180 mg once daily with a seven-day lead in at 90 mg once daily achieving an overall response and a median duration of response greater than one year. Importantly, the extent of activity among those with brain metastases was also notable."

"For patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib, who are facing the uncertainty of disease progression and the potentially devastating impact of brain metastases, the approval of Alunbrig offers a new hope," Bonnie Addario, founder and chair of the Addario Lung Cancer Foundation said.

 "Today’s FDA approval of Alunbrig is an important milestone in the treatment of patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib," Christophe Bianchi, M.D., President, Takeda Oncology said. "Takeda is committed to the continued development of Alunbrig around the globe and to bringing this important therapy to more patients in need."

The FDA approval of Alunbrig was primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of brigatinib in adults. This ongoing, two-arm, open-label, multicenter trial enrolled 222 patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib. Patients received either 90 mg of Alunbrig once daily (n=112) or 180 mg once daily following a seven-day lead-in of 90 mg once daily (n=110). The major efficacy outcome measure was confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by an Independent Review Committee (IRC). Additional efficacy outcome measures included Investigator-assessed ORR, duration of response (DOR), intracranial ORR, and intracranial DOR.

The recommended dosing regimen for Alunbrig is 90 mg orally once daily for the first 7 days. If 90 mg is tolerated during the first 7 days, increase the dose to 180 mg orally once daily.

With a median follow-up of 8 months (range 0.1 - 20.2), results demonstrated that of the patients who received the recommended dosing regimen (90→180 mg), 53 percent achieved a confirmed overall response (OR) as assessed by IRC and 54 percent as assessed by Investigator. At the recommended dosing regimen, the median duration of response was 13.8 months as assessed by IRC and 11.1 months by Investigator assessment. Additionally, at the recommended dosing regimen, 67 percent of patients with measurable brain metastases (n=18) achieved a confirmed intracranial OR by IRC assessment.

Among the 23 patients who exhibited an intracranial response, 78% of patients in the 90 mg arm and 68% of patients in the 90→180 mg group maintained a response for at least four months.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 222,500 new cases of lung cancer diagnosed each year in the United States, according to the American Cancer Society. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients as well. Approximately two to eight percent of patients with NSCLC have a rearrangement in the ALK gene.